Fucoidan compositions and methods for dietary and nutritional supplements

ABSTRACT

Compositions and methods relating to partially hydrolyzed fucoidan for use in dietary supplements are described. Fucoidan from brown seaweeds is partially hydrolyzed and then mixed with other ingredients for use as a dietary supplement in beverage, capsule, or tablet form. The fucoidan is partially hydrolyzed with acid and heat. The partially hydrolyzed fucoidan can also be sulfonated. Other ingredients that can be included in the dietary supplement include high-ORAC-value antioxidants, minerals, pepper extract, flavoring agents, coloring agents, and preservatives. The compositions can be in the form of beverages, tablets, capsules, powders, and the like.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/083,826, filed Mar. 18, 2005, now U.S. Pat. No. 7,749,545, which ishereby incorporated by reference in its entirety.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

BACKGROUND OF THE INVENTION

This invention relates generally to dietary supplements incorporatingfucoidan derived from seaweed. More particularly, the present inventionrelates to dietary supplements incorporating fucoidan from seaweed, suchas Tongan limu moui and Japanese hoku kombu and mozuku, and optionallyincluding one or more ingredients having a high oxygen radicalabsorbance capacity (ORAC).

Fucoidan is a sulfated polysaccharide found in many sea plants andanimals and is particularly concentrated in the cell walls of brownalgae (Phaeophyceae). Fucoidan is a complex carbohydrate polymercomposed mostly of sulfated L-fucose residues. These polysaccharides areeasily extracted from the cell wall of brown algae with hot water ordilute acid and can account for more than 40% of the dry weight ofisolated cell walls. O. Berteau & B. Mulloy, Sulfated fucans, freshperspectives: structures, functions, and biological properties ofsulfated fucans and an overview of enzymes active toward this class ofpolysaccharide, 13 Glycobiology 29R-40R (2003). Fucoidan structureappears to be linked to algal species, but there is insufficientevidence to establish any systematic correspondence between structureand algal order. High amounts of α(1-3) and α(1-4) glycosidic bondsoccur in fucoidans from Ascophyllum nodosum. A disaccharide repeatingunit of alternating α(1-3) and α(1-4) bonds represents the most abundantstructural feature of fucoidans from both A. nodosum and Fucusvesiculosus. Sulfate residues are found mainly in position 4. Furtherheterogeneity is added by the presence of acetyl groups coupled tooxygen atoms and branches, which are present in all the plant fucoidans.

Fucoidan-containing seaweeds have been eaten and used medicinally for atleast 3000 years in Tonga and at least 2000 years in China. An enormousamount of research has been reported in the modern scientificliterature, where more than 500 studies are referenced in a PubMedsearch for fucoidan.

The physiological properties of fucoidans in the algae appear to be arole in cell wall organization and possibly in cross-linking of alginateand cellulose and morphogenesis of algal embryos. Fucoidans also have awide spectrum of activity in biological systems. They have anticoagulantand antithrombotic activity, act on the inflammation and immune systems,have antiproliferative and antiadhesive effects on cells, and protectcells from viral infection.

Further, fucoidan has numerous beneficial functions that heal andstrengthen different systems of the body, including anti-viral,anti-inflammatory, anti-coagulant, and anti-tumor properties. A. I. Usovet al., Polysaccharides of Algae: Polysaccharide Composition of SeveralBrown Algae from Kamchatka, 27 Russian J. Bio. Chem. 395-399 (2001).Fucoidan has been found to build and stimulate the immune system.Research has also indicated that fucoidan reduces allergies, inhibitsblood clotting, fights diabetes by controlling blood sugar, preventsulcers, relieves stomach disorders, reduces inflammation, protects thekidneys by increasing renal blood flow, and detoxifies the body.Fucoidan also helps to reduce and prevent cardiovascular disease bylowering high cholesterol levels and activating enzymes involved in thebeta-oxidation of fatty acids.

A Japanese study found that fucoidans enhanced phagocytosis, the processin which white blood cells engulf, kill, digest, and eliminate debris,viruses, and bacteria. An American study reported that fucoidansincreased the number of circulating mature white blood cells. AnArgentine study and a Japanese study found that fucoidans inhibitedviruses, such as herpes simplex type I, from attaching to, penetrating,and replicating in host cells. A Swedish study is among the many thatshowed fucoidans inhibit inflammation cascades and tissue damage thatmay lead to allergies. Other studies, such as one in Canada, found thatfucoidans block the complement activation process that is believed toplay an adverse role in chronic degenerative diseases, such asatherosclerosis, heart attack, and Alzheimer's disease. Two Americanstudies found that fucoidans increase and mobilize stem cells.

Researchers have also determined that fucoidan tends to combat cancer byreducing angiogenesis (blood vessel growth), inhibiting metastasis(spreading of cancer cells to other parts of the body), and promotingdeath of cancer cells. Certain societies that make brown seaweed part oftheir diet appear to have remarkably low instances of cancer. Forexample, the prefecture of Okinawa, where the inhabitants enjoy some ofthe highest life expectancies in Japan, also happens to have one of thehighest per capita consumption rates of fucoidans. It is noteworthy thatthe cancer death rate in Okinawa is the lowest of all the prefectures inJapan.

Brown seaweed is found in abundance in various ocean areas of the world.One of the purest locations that provides some of the highest yields offucoidan is in the clear waters surrounding the Tongan islands, wherethe seaweed is called limu moui. In Japan, hoku kombu (Laminariajaponica), is said to be particularly rich in fucoidans and is similarto limu moui. The Japanese also consume at least two other types ofbrown seaweed—wakame and mozuku (Cladosiphon and Nemacystus).

Typically, about four percent by weight of Tongan limu moui is fucoidan.There are at least three types of fucoidan polymer molecules found inbrown seaweed. U-fucoidan, having about 20 percent glucuronic acid, isparticularly active in carrying out cancer cell destruction. F-fucoidan,a polymer of mostly sulfated fucose, and G-fucoidan both tend to inducethe production of HGF cells that assist in restoring and repairingdamaged cells. All three types of fucoidan also tend to induce theproduction of agents that strengthen the immune system.

Accordingly, consumable beverages and other compositions of fucoidan areneeded to benefit from the many advantages mentioned above. Methods ofpreparation of fucoidan may be used to enhance consumption while notdestroying its beneficial effects.

In view of the foregoing, it will be appreciated that providing afucoidan-containing nutritional supplement would be a significantadvancement in the art.

BRIEF SUMMARY OF THE INVENTION

Dietary supplements according to the present invention provide manybeneficial effects, among them providing for life extension, anti-aging,and regeneration of cells and tissues, such as muscles and bones;promoting growth factors in the body; promoting high energy, vitality,and youthfulness; preventing blood clots and thrombosis; reducing andpreventing inflammation; strengthening the immune system; protectingagainst viral, bacterial, and other types of infection; preventingtumorigenesis and the spread of cancers; reducing allergies; fightingdiabetes by controlling blood sugar; preventing ulcers; relievingstomach disorders; protecting the kidneys by increasing renal bloodflow; detoxifing the body; reducing and preventing cardiovasculardisease; and activating stem cells.

An illustrative embodiment of a dietary supplement according to thepresent invention comprises about 0.5 to about 70 parts by weight ofpartially hydrolyzed fucoidan and about 30 to about 99.5 parts by weightof water. The partially hydrolyzed fucoidan can be sulfonated or notduring the hydrolysis reaction. Sulfonated fucoidan is believed toprovide certain benefits to the dietary supplement, such as enhancedproperties relating to anti-cancer, antimicrobial, anti-inflammation,life extension, anti-aging, cell and tissue regeneration, and stem cellactivation effects. Additional illustrative embodiments further compriseother ingredients, which optionally may be added in any selectedcombination. For example, a dietary supplement may additionally compriseabout 0.5 to about 20 parts by weight of a nutraceutical ingredienthaving a high ORAC value, such as concentrates of black grapes, redgrapes, white grapes, blueberry, acai fruit, raspberry, blackberry,strawberry, plum, orange, cherry, kiwi fruit, currant, elderberry, blackcurrant, cranberry, mangosteen, noni, aronia, wolfberry,proanthocyanidins (such as from grape seed extract), curcuminoids, ormixtures thereof. Further, a dietary supplement may further compriseabout 0.01 to about 2 parts by weight of minerals, such as deep seaminerals. Still further, a dietary supplement may further comprise about0.001 to about 1 parts by weight of pepper extract, such as black pepperor Sichuan pepper extract or mixtures thereof. The fucoidan from whichthe partially hydrolyzed fucoidan is made can be from Tongan limu mouiseaweed or Japanese mozuku or kombu seaweeds, or a mixture of suchfucoidans. The dietary supplement can additionally comprise flavoringagents, preservatives, and the like.

Another illustrative dietary supplement according to the presentinvention comprises about 0.5 to about 70 parts by weight of partiallyhydrolyzed fucoidan, about 0.5 to about 20 parts by weight of anutraceutical ingredient having a high ORAC value and about 10 to about99 parts by weight of water.

Still another illustrative dietary supplement according to the presentinvention comprises about 0.5 to about 70 parts by weight of partiallyhydrolyzed fucoidan, about 0.001 to about 1 parts by weight of pepperextract, and about 29 to about 99.5 parts by weight of water.

Yet another illustrative dietary supplement according to the presentinvention comprises about 0.5 to about 70 parts by weight of partiallyhydrolyzed, sulfonated fucoidan, about 0.001 to about 1 parts by weightof pepper extract, about 0.5 to about 20 parts by weight of anutraceutical ingredient having a high ORAC value, and about 9 to about99.0 parts by weight of water.

A still further illustrative embodiment of the invention comprises asolid dosage form for providing a dietary supplement, the dosage formcomprising partially hydrolyzed fucoidan. This solid dosage formillustratively comprises a tablet, capsule, or spray dried or freezedried powder. The solid dosage form can additionally contain any of theingredients described above in connection with the liquid forms of thedietary supplement. In addition, the solid dosage forms can containpharmaceutical necessities useful for the manufacture and compoundingthereof.

Another illustrative embodiment of the invention comprises a method ofmaking a partially hydrolyzed fucoidan composition, the methodcomprising:

(a) mixing a selected amount of fucoidan-containing seaweed with waterand adjusting the hydrogen ion concentration corresponding to a pH ofabout 2.0 to pH 4.0 to result in a mixture;

(b) while continuing to mix the mixture, heating the mixture to about37° C. to about 95° C. for a selected time period, thereby partiallyhydrolyzing the fucoidan in the seaweed and resulting in a heatedmixture;

(c) cooling the heated mixture to ambient temperatures while continuingto mix the heated mixture as it cools, resulting in a cooled mixture;and

(d) incubating the cooled mixture at ambient temperatures while mixingfor up to about 72 hours, thereby obtaining the partially hydrolyzedfucoidan composition. The hydrogen ion concentration is typicallyadjusted by adding an acid, according to methods well known in the art.An illustrative acid comprises sulfuric acid, and when sulfuric acid isused, the conditions can be selected such that available reactive groupscreated by the partial hydrolysis of the fucoidan are sulfonated,resulting in a partially hydrolyzed, sulfonated fucoidan composition.The heating of the mixture can be carried out at increased pressure,i.e. at greater than one atmosphere of pressure, to speed up thehydrolysis reaction.

Still another illustrative embodiment of the invention comprises amethod of making a dietary supplement, the method comprising:

(a) mixing about 0.5 to about 70 parts by weight of a partiallyhydrolyzed fucoidan composition with about 30 to about 99.5 parts byweight of water to result in a mixture;

(b) sterilizing the mixture; and

(c) packaging the sterilized mixture in a suitable container. Additionalingredients can be added to the mixture, as described above. Sterilizingthe mixture can be carried out by pasteurizing the mixture or treatingthe mixture with a high temperature short time (HTST) process or anultra-high temperature (UHT) process. Packaging the sterilized mixturecan comprise a hot-fill process or a cold-fill process.

DETAILED DESCRIPTION

Before the present fucoidan-containing dietary supplements and methodsare disclosed and described, it is to be understood that this inventionis not limited to the particular configurations, process steps, andmaterials disclosed herein as such configurations, process steps, andmaterials may vary somewhat. It is also to be understood that theterminology employed herein is used for the purpose of describingparticular embodiments only and is not intended to be limiting since thescope of the present invention will be limited only by the appendedclaims and equivalents thereof.

The publications and other reference materials referred to herein todescribe the background of the invention and to provide additionaldetail regarding its practice are hereby incorporated by reference. Thereferences discussed herein are provided solely for their disclosureprior to the filing date of the present application. Nothing herein isto be construed as an admission that the inventors are not entitled toantedate such disclosure by virtue of prior invention.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to a dietary supplement containing “a partially hydrolyzedfucoidan” includes a mixture of two or more of such partially hydrolyzedfucoidans, reference to “an acid” includes reference to two or more ofsuch acids, and reference to “a preservative” includes reference to amixture of two or more of such preservatives.

In describing and claiming the present invention, the followingterminology will be used in accordance with the definitions set outbelow.

As used herein, “comprising,” “including,” “containing,” “characterizedby,” and grammatical equivalents thereof are inclusive or open-endedterms that do not exclude additional, unrecited elements or methodsteps. “Comprising” is to be interpreted as including the morerestrictive terms “consisting of” and “consisting essentially of.”

As used herein, “partially hydrolyzed fucoidan” means fucoidan that hasbeen hydrolyzed into smaller polymers and oligomers, but not sothoroughly hydrolyzed as to result in complete hydrolysis tomonosaccharides.

As used herein, “high ORAC value” or similar terms means an ORAC valueof at least about 400 per 100 grams of fruit or vegetable. For example,blueberries have an ORAC value of about 2,400 per 100 grams, and thefollowing fruits have ORAC values as shown in parentheses per 100 grams:blackberries (2,036), cranberries (1,750), strawberries (1,540),raspberries (1,220), plums (949), oranges (750), red grapes (739)cherries (670), kiwi fruit (602), and white grapes (446). Other fruitsknown to have a high ORAC value include black grapes, mangosteen, noni,aronia, wolfberry, and acai, and the like. Further, nutraceuticalingredients known to have high ORAC values include proanthocyanidins,such as from extracts of grape seed and bark of white pine of southernEurope (e.g., pycnogenol, U.S. Pat. No. 4,698,360), and curcuminoids.Oligomeric proanthocyanidins (OPC) are illustrative.

As used herein, “sterilizing” and similar terms means, with respect tonutritional supplements having a pH less than 4.6 and a water activitygreater than 0.85, pasteurizing the nutritional supplement and storingat room temperature. With respect to nutritional supplements having a pHgreater than 4.6 and a water activity greater than 0.85, “sterilizing”and similar terms mean applying heat such that the nutritionalsupplement is rendered free of microorganisms capable of reproducing inthe nutritional supplement under normal non-refrigerated conditions ofstorage and distribution.

As used herein, “pasteurization” traditionally means a process namedafter scientist Louis Pasteur by which every particle of milk is heatedto not lower than 62.8° C. (i.e., 145° F.) for not less than 30 minutesand promptly cooled to destroy any harmful bacteria that may be presentwithout affecting flavor and food value. Currently, the most commonmethod of pasteurization in the United States is High Temperature ShortTime (HTST) pasteurization, which uses metal plates and hot water toraise temperatures to 71.7° C. (i.e., 161° F.) for not less than 15seconds, followed by rapid cooling. Ultra Pasteurization (UP) is aprocess similar to HTST pasteurization, but using higher temperaturesand longer times. UP pasteurization results in a product with longershelf life but still requiring refrigeration of milk, but not ofacidified foods or nutritional supplements (pH <4.6). Another method,Ultra High Temperature (UHT) pasteurization, raises the temperature toover 93.3° C. (i.e., 200° F.) for a few seconds, followed by rapidcooling. A UHT-pasteurized product that is packaged aseptically resultsin a “shelf stable” product that does not require refrigeration until itis opened.

As used herein, “aseptic processing and packaging” and similar termsmean the filling of a sterilized cooled product into pre-sterilizedcontainers, followed by aseptic hermetic sealing, with a pre-sterilizedclosure, in an atmosphere free of microorganisms.

As used herein, “hermetically sealed container” and similar terms mean acontainer that is designed and intended to be secure against the entryof microorganisms and thereby to maintain the sterility of its contentsafter processing.

As used herein, “tablets” are solid dosage forms containing a dietarysupplement with or without suitable excipients or diluents and preparedeither by compression or molding methods well known in the art. Tabletshave been in widespread use since the latter part of the 19^(th) centuryand their popularity continues. Tablets remain popular as a dosage formbecause of the advantages afforded both to the manufacturer (e.g.,simplicity and economy of preparation, stability, and convenience inpackaging, shipping, and dispensing) and the user (e.g., accuracy ofdosage, compactness, portability, blandness of taste, and ease ofadministration). Although tablets are most frequently discoid in shape,they may also be round, oval, oblong, cylindrical, or triangular. Theymay differ greatly in size and weight depending on the amount of dietarysupplement present and the intended method of administration. They aredivided into two general classes, (1) compressed tablets, and (2) moldedtablets or tablet triturates. In addition to the active or therapeuticingredient or ingredients, tablets contain a number or inert materialsor additives. A first group of such additives includes those materialsthat help to impart satisfactory compression characteristics to theformulation, including diluents, binders, and lubricants. A second groupof such additives helps to give additional desirable physicalcharacteristics to the finished tablet, such as disintegrators, colors,flavors, and sweetening agents.

As used herein, “diluents” are inert substances added to increase thebulk of the formulation to make the tablet a practical size forcompression. Commonly used diluents include calcium phosphate, calciumsulfate, lactose, kaolin, mannitol, sodium chloride, dry starch,powdered sugar, silica, and the like.

As used herein, “binders” are agents used to impart cohesive qualitiesto the powdered material. Binders, or “granulators” as they aresometimes known, impart a cohesiveness to the tablet formulation, whichinsures the tablet remaining intact after compression, as well asimproving the free-flowing qualities by the formulation of granules ofdesired hardness and size. Materials commonly used as binders includestarch; gelatin; sugars, such as sucrose, glucose, dextrose, molasses,and lactose; natural and synthetic gums, such as acacia, sodiumalginate, extract of Irish moss, panwar gum, ghatti gum, mucilage ofisapol husks, carboxymethylcellulose, methylcellulose,polyvinylpyrrolidone, Veegum, microcrystalline cellulose,microcrystalline dextrose, amylose, and larch arabogalactan, and thelike.

As used herein, “lubricants” are materials that perform a number offunctions in tablet manufacture, such as improving the rate of flow ofthe tablet granulation, preventing adhesion of the tablet material tothe surface of the dies and punches, reducing interparticle friction,and facilitating the ejection of the tablets from the die cavity.Commonly used lubricants include talc, magnesium stearate, calciumstearate, stearic acid, and hydrogenated vegetable oils.

As used herein, “disintegrators” or “disintegrants” are substances thatfacilitate the breakup or disintegration of tablets afteradministration. Materials serving as disintegrants have been chemicallyclassified as starches, clays, celluloses, algins, or gums. Otherdisintegrators include Veegum HV, methylcellulose, agar, bentonite,cellulose and wood products, natural sponge, cation-exchange resins,alginic acid, guar gum, citrus pulp, cross-linked polyvinylpyrrolidone,carboxymethylcellulose, and the like.

As used herein, “coloring agents” are agents that give tablets a morepleasing appearance, and in addition help the manufacturer to controlthe product during its preparation and help the user to identify theproduct. Any of the approved certified water-soluble FD&C dyes, mixturesthereof, or their corresponding lakes may be used to color tablets. Acolor lake is the combination by adsorption of a water-soluble dye to ahydrous oxide of a heavy metal, resulting in an insoluble form of thedye.

As used herein, “flavoring agents” vary considerably in their chemicalstructure, ranging from simple esters, alcohols, and aldehydes tocarbohydrates and complex volatile oils. Natural and synthetic flavorsof almost any desired type are now available.

As used herein, “capsules” are solid dosage forms in which the dietarysupplement is enclosed in a hard or soft (including gel caps), solublecontainer or shell of a suitable polymer, such as gelatin. The softgelatin capsule was invented by Mothes, a French pharmacist in 1833.During the following year DuBlanc obtained a patent for his soft gelatincapsules. In 1848 Murdock patented the two-piece hard gelatin capsule.The encapsulation of medicinal agents, dietary supplements, and the likeremains a popular method of administering agents by the oral route.Capsules are tasteless, easily administered, and easily filled. Somepersons find it easier to swallow capsules than tablets, thereforepreferring to take this form when possible. This preference has promptedmanufacturers to market products in capsule form even though the producthas already been produced in tablet form.

As used herein, “pharmaceutical necessities” means substances that areof little or no dietary or therapeutic value, but which are useful inthe manufacture and compounding of various dietary supplementpreparations. These substances include antioxidants and preservatives;coloring, flavoring, and diluting agents; emulsifying and suspendingagents; ointment bases; pharmaceutical solvents; and miscellaneousagents. See, for example, Remington's Pharmaceutical Sciences for areview of what is known in the art concerning pharmaceuticalnecessities.

As used here, “powders” means a solid dosage form intended to besuspended or dissolved in water or another liquid or mixed with softfoods prior to administration. Powders are typically prepared by spraydrying or freeze drying of liquid formulations. Powders are advantageousdue to flexibility, stability, rapid effect, and ease of administration.

As used herein, “Brix” is a scale for measuring the sugar content ofgrapes, wine, and the like. Each degree of Brix is equivalent to onegram of sugar per 100 ml of liquid. Thus, an 18 degree Brix sugarsolution contains 18% by weight of sugar. Brix also describes thepercent of suspended solids in a liquid. Thus, 95 Brix, for example,denotes a liquid that contains 95% by weight of suspended solids. Brixis measured with an optical device called a refractometer. The Brixsystem of measurement is named for A. F. W. Brix, a 19^(th) centuryGerman inventor.

The present invention advances prior art dietary supplements byproviding a dietary supplement formulated with fucoidan from seaweed,such as limu moui, kombu, or mozuku. The addition of fucoidan to thedietary supplement of the present invention serves to providesignificant dietary and nutritional advantages not found in prior artdietary supplements. The fucoidan-enhanced dietary supplement of thepresent invention provides many beneficial functions, includingproviding for life extension, anti-aging, and regeneration of cells andtissues, such as muscles and bones; promoting growth factors in thebody; promoting high energy, vitality, and youthfulness; maintaining andstrengthening the immune system, reducing allergies, inhibiting bloodclotting, controlling blood sugar, preventing ulcers, reliving stomachdisorders, reducing inflammation, protecting the kidneys, anddetoxifying the body. Fucoidan preparations according to the presentinvention may also help to reduce and prevent cardiovascular disease bylowering cholesterol levels, inhibiting smooth muscle cellproliferation, and activating enzymes involved in the beta-oxidation offatty acids.

In addition, the fucoidan-enhanced dietary supplement of the presentinvention fights cancerous tumors and minimizes the visible signs ofboth biological and environmental aging. That is, the present dietarysupplements slow the aging process assist in regenerating damaged cellsand tissues, and promote growth factors in the body. Fucoidan is high inantioxidants that help to fight free radical damage to the body that maylead to cancer. Fucoidan also provides significant benefits to the skin.Fucoidan is high in antioxidants that help to fight free radical damagecaused by the sun and other changing environmental conditions andelements.

Brown seaweed grows in many oceans, including off the coasts of Japanand Okinawa, Russian coastal waters, Tonga, and other places. Anexcellent source of fucoidan is the limu moui sea plant growing in thewaters of the Tongan islands. This brown seaweed contains many vitamins,minerals, and other beneficial substances and is particularly rich infucoidan.

Typically, the brown seaweed grows in long angel hair stems withnumerous leaves. The fucoidan ingredient is found in naturalcompositions on the cell walls of the seaweed, providing a slipperysticky texture that protects the cell walls from the sunlight.

In one embodiment, a kombu-type or mozuku-type seaweed is harvested fromthe coastal waters of the Tongan islands. These seaweeds are typicallymanually harvested , including stems and leaves, by divers and cleanedto remove extraneous materials. The seaweed is then usually frozen inlarge containers and shipped to a processing plant.

In processing, the heavy outer fibers must first be broken down toprovide access to the fucoidan component. If frozen, the seaweedmaterial is first thawed, but if not frozen, then the seaweed materialis placed in a mixing vat and shredded, while being hydrolyzed withacids and water. The material can optionally be sulfonated with sulfuricacid to help in breaking down the heavy cell fibers. The mixture is alsobuffered with citric acid and thoroughly blended to maintain suspension.The material may also be heated at atmospheric or greater thanatmospheric pressure while mixing. The resulting puree is tested andmaintained at a pH of about 2 to 4 so as to remain acidic, enhancingpreservative and stability characteristics.

The puree may be used in preparing dietary supplement products.Alternately, the mixture may be refrozen in small containers for laterprocessing.

The present invention provides a dietary supplement beverage formulatedwith fucoidan compositions from seaweed, such as the limu moui seaweedplant. The fucoidan compositions are present in selected embodimentsfrom about 0.5 to about 70 percent by weight of the total weight of thecomposition. Other ingredients may include an antioxidant, such a acaifruit and blueberry having a high oxygen radical absorbance capacity(ORAC). Such antioxidants may be present in amounts from about 0 toabout 20 percent by weight. Additionally, minerals such as deep seaminerals may be present in an amount from about 0 to about 2 percent byweight, to provide important minerals.

High ORAC Nutraceutical Ingredients

Free radicals are very reactive and highly destructive compounds in thebody. Free radicals are products of oxidative deterioration of suchsubstances as polyunsaturated fat. Antioxidants convert free radicalinto a less reactive and nonharmful chemical form. Antioxidants that canbe used in dietary supplements include β-carotene, vitamin E, vitamin C,N-acetyl cysteine, α-lipoic acid, selenium, and the like. Antioxidantshaving a high ORAC value are particularly desirable. Illustratively,nutraceutical antioxidants of high ORAC value that can be used in thepresent invention include concentrates of grape (red, black, or white),blueberry, acai fruit, raspberry, blackberry, strawberry, plum, orange,cherry, kiwi fruit, currant, elderberry, black currant, cranberry,mangosteen, noni, aronia, wolfberry, and mixtures thereof. Other highORAC nutraceutical ingredients include proanthocyanidins, such asoligomeric proanthocyanidins, curcuminoids, and the like.

Minerals

Minerals serve a wide variety of essential physiological functionsranging from structural components of body tissues to essentialcomponents of many enzymes and other biological important molecules.Minerals are classified as micronutrients or trace elements on the basisof the amount present in the body. The seven micronutrients (calcium,potassium, sodium, magnesium, phosphorus, sulfur, and chloride) arepresent in the body in quantities of more than five grams. Traceelements, which include boron, copper, iron, manganese, selenium, andzinc are found in the body in quantities of less than five grams.

Micronutrient Minerals. Calcium is the mineral element believed to bemost deficient in the diet in the United States. Calcium intakes inexcess of 300 mg per day are difficult to achieve in the absence of milkand dairy products in the diet. This is far below the recommendeddietary allowance (RDA) for calcium (1000 mg per day for adults andchildren ages one to ten, 1200 mg per day for adolescents and pregnantand lactating women, which equates to about four glasses of milk perday). In fact, it has been reported that the mean daily calcium intakefor females over age 12 does not exceed 85 percent of the RDA. Inaddition, during the years of peak bone mass development (18 to 30),more than 66 percent of all U.S. women fail to consume the recommendedamounts of calcium on any given day. After age 35, this percentageincreases to over 75 percent.

Although the general public is not fully aware of the consequences ofinadequate mineral intake over prolonged periods of time, there isconsiderable scientific evidence that low calcium intake is one ofseveral contributing factors leading to osteoporosis. In addition, thedietary ratio of calcium to phosphorous (Ca:P) relates directly to bonehealth. A Ca to P ratio of 1:1 to 2:1 is recommended to enhance bonemarrowization in humans. Such ratios are difficult to achieve absent anadequate dietary supply of milk and dairy products, or an adequatesupply of calcium and other minerals for the lactose-intolerant segmentof the population.

Magnesium is the second most plentiful cation of the intracellularfluids. It is essential for the activity of many enzyme systems andplays an important role with regard to neurochemical transmission andmuscular excitability. Deficits are accompanied by a variety ofstructural and functional disturbances. The average 70-kg adult hasabout 2000 mEq of magnesium in his body. About 50% of this magnesium isfound in bone, 45% exists as an intracellular cation, and 5% is in theextracellular fluid. About 30% of the magnesium in the skeletonrepresents an exchangeable pool present either within the hydrationshell or on the crystal surface. Mobilization of the cation from thispool in bone is fairly rapid in children, but not in adults. The largerfraction of magnesium in bone is apparently an integral part of bonecrystal.

The average adult in the United States ingests about 20 to 40 mEq ofmagnesium per day in an ordinary diet, and of this about one third isabsorbed from the gastrointestinal tract. The evidence suggests that thebulk of the absorption occurs in the upper small bowel. Absorption is bymeans of an active process apparently closely related to the transportsystem for calcium. Ingestion of low amounts of magnesium results inincreased absorption of calcium and vice versa.

Magnesium is a cofactor of all enzymes involved in phosphate transferreactions that utilize adenosine triphosphate (ATP) and other nucleotidetriphosphates as substrates. Various phosphatases and pyrophosphatasesalso represent enzymes from an enormous list that are influenced by thismetallic ion.

Magnesium plays a vital role in the reversible association ofintracellular particles and in the binding of macromolecules tosubcellular organelles. For example, the binding of messenger RNA (mRNA)to ribosomes is magnesium dependent, as is the functional integrity ofribosomal subunits. Certain of the effects of magnesium on the nervoussystem are similar to those of calcium. An increased concentration ofmagnesium in the extracellular fluid causes depression of the centralnervous system (CNS). Hypomagnesemia causes increased CNS irritability,disorientation, and convulsions. Magnesium also has a direct depressanteffect on skeletal muscle. Abnormally low concentrations of magnesium inthe extracellular fluid result in increased acetylcholine release andincreased muscle excitability that can produce tetany.

Trace Elements. Boron is required by the body in trace amounts forproper metabolism of calcium, magnesium, and phosphorus. Boron helpsbrain function, healthy bones, and can increase alertness. Boron is alsouseful for people who want to build muscle. Boron is known to helpprevent postmenopausal osteoporosis. Further, a relationship has beenshown between a lack of boron in the diet and the chances of developingarthritis. R. E. Newnham, 46 Journal of Applied Nutrition (1994).

Chromium is an important trace element wherein the lack of sufficientchromium in the diet leads to impairment of glucose utilization,however, disturbances in protein and lipid metabolism have also beenobserved. Impaired glucose utilization occurs in many middle-aged andelderly human beings. In experimental studies, significant numbers ofsuch persons have shown improvement in their glucose utilization aftertreatment with chromium. Chromium is transported by transferrin in theplasma and competes with iron for binding sites. Chromium as a dietarysupplement may produce benefits due to its enhancement of glucoseutilization and its possible facilitating the binding of insulin toinsulin receptors, which increases its effects on carbohydrate and lipidmetabolism. Chromium as a supplement may produce benefits inatherosclerosis, diabetes, rheumatism, and weight control.

Copper is another important trace element in the diet. The most commondefect observed in copper-deficient animals is anemia. Otherabnormalities include growth depression, skeletal defects, demyelinationand degeneration of the nervous system, ataxia, defects in pigmentationand structure of hair or wool, reproductive failure and cardiovascularlesions, including dissecting aneurisms. Several copper-containingmetalloproteins have been isolated, including tyrosinase, ascorbic acidoxidase, laccase, cytochrome oxidase, uricase, monoamine oxidase,δ-aminolevulinic acid hydrydase, and dopamine-β-hydroxylase. Copperfunctions in the absorption and utilization of iron, electron transport,connective tissue metabolism, phospholipid formation, purine metabolism,and development of the nervous system. Ferroxidase I (ceruloplasmin), acopper-containing enzyme, effects the oxidation of Fe(II) to Fe(III), arequired step for mobilization of stored iron. A copper-containingenzyme is thought to be responsible for the oxidative deamination of theepsilon amino group of lysine to produce desmosine and isodesmosine, thecross-links of elastin. In copper-deficient animals the arterial elastinis weaker and dissecting aneurisms may occur.

Iodine is important for the production of thyroid hormones, whichregulate cellular oxidation. The iodine-deficiency disease is goiter. Iniodine-deficient young, growth is depressed and sexual development isdelayed, the skin and hair are typically rough, and the hair becomesthin. Cretinism, feeble-mindedness, and deaf-mutism occur in a severedeficiency. There is reproductive failure in females and decreasedfertility in males that lack sufficient iodine in the diet.

Iron is an essential component of several important metalloproteins.These include hemoglobin, myoglobin, and many oxidation-reductionenzymes. In iron deficiency, there may be reduced concentrations of someof the iron-containing enzymes, such as cytochrome c in liver, kidney,and skeletal muscle, and succinic dehydrogenase in the kidney and heart.

Manganese plays a role in the synthesis of GAGs, collagen, andglycoproteins, which are important constituents of cartilage and bone.Manganese is required for enzyme activity of glycosyltransferases. Thisfamily of enzymes is responsible for linking sugars together into GAGs,adding sugars to other glycoproteins, adding sulfate to aminosugars,converting sugars to other modified sugars, and adding sugars to lipids.These functions are manifested as GAG synthesis (hyaluronic acid,chondroitin sulfate, karatan sulfate, heparin sulfate, and dermatinsulfate, among others), collagen synthesis, and function of many otherglycoproteins and glycolipids. GAGs and collagen are chief structuralelements for all connective tissues. Their synthesis is essential forproper maintenance and repair of connective tissues.

Manganese deficiencies in humans and animals lead to abnormal bonegrowth, swollen and enlarged joints, and slipped tendons. In humans,manganese deficiencies are associated with bone loss, arthritis, andimpaired glucose utilization. Levels of all GAGs are decreased inconnective tissues during manganese deficiencies, with chondroitinsulfates being most depleted. Manganese-deficient organisms quicklynormalize GAG and collagen synthesis when manganese is provided.

Manganese is also required for activity of manganese superoxidedismutase (MnSOD), which is present only in mitochondria. Manganesedeficiency decreases the activity of MnSOD and may lead to mitochondrialdysfunction, manifested as decreased cellular functions. Manganese isrequired for the conversion of mevalonic acid to squalene. Pyruvatecarboxylase is a manganese metalloenzyme, repressible by insulin,important in the citric acid cycle for the oxidation of carbohydrates,lipids, and proteins, as well as in the synthesis of glucose and lipids.

Molybdenum is an essential mineral found in highest concentrations inthe liver, kidneys, skin, and bones. This mineral is required by thebody to properly metabolize nitrogen. It is also a vital component ofthe enzyme xanthine oxidase, which is required to convert purines touric acid, a normal byproduct of metabolism. Molybdenum also supportsthe body's storage of iron and other cellular functions such as growth.A deficiency of molybdenum is associated with mouth and gum disordersand cancer. A diet high in refined and processed foods can lead to adeficiency of molybdenum, resulting in anemia, loss of appetite andweight, and stunted growth in animals. While these deficiencies have notbeen observed directly in humans, it is known that a molybdenumdeficiency can lead to impotence in older males.

Selenium is an essential trace element that functions as a component ofenzymes involved in protection against antioxidants and thyroid hormonemetabolism. In several intra- and extra-cellular glutathione peroxidasesand iodothyronine 5′-deiodinases, selenium is located at the activecenters as the selenoamino acid, selenocysteine (SeCYS). At least twoother proteins of unknown function also contain SeCYS. Although SeCYS isan important dietary form, it is not directly incorporated into thesespecific selenium-proteins; instead, a co-translational process yieldstRNA-bound SeCYS. In contrast, selenium as seleno-methionine isincorporated non-specifically into many proteins, as it competes withmethionine in general protein synthesis. Therefore, tissues oftencontain both specific, as well as the nonspecific, selenium-containingproteins when both SeCYS and selenomethionine are consumed, as found inmany foods. Selenium is a major antioxidant nutrient and is involved inprotecting cell membranes and preventing free radical generation,thereby decreasing the risk of cancer and disease of the heart and bloodvessels. Medical surveys show that increased selenium intake decreasesthe risk of breast, colon, lung and prostate cancer. Selenium alsopreserves tissue elasticity; slows down the aging and hardening oftissues through oxidation; and helps in the treatment and prevention ofdandruff. Recent research has shown antitumorigenic effects of highlevels of selenium in the diets of several animal models.

Vanadium is an essential nutrient beneficial for thyroid hormonemetabolism. The daily requirement necessary to prevent a deficiency isabout 10 to 20 micrograms a day. Vanadium deficiency can lead to slowgrowth, defective bones, and altered lipid metabolism. Vanadium exertsan insulin-like effect in some respects, and there has been aconsiderable amount of research on vanadium and diabetes. In insulindependent diabetics, vanadium has been found to reduce the amount ofinsulin required to manage the disease, and in non-insulin dependentdiabetics, vanadium has been known to control the condition altogether.Research has shown that supplementation with vanadium leads to anincrease in glucose transport into cells, which suggests that vanadiumsupplementation of the diet improves glucose metabolism and may aid inpreventing diabetes.

Zinc is known to occur in many important metalloenzymes. These includecarbonic anhydrase, carboxypeptidases A and B, alcohol dehydrogenase,glutamic dehydrogenase, D-glyceraldehyde-3-phosphate dehydrogenase,lactic dehydrogenase, malic dehydrogenase, alkaline phosphatase, andaldolase. Impaired synthesis of nucleic acids and proteins has beenobserved in zinc deficiency. There is also evidence that zinc may beinvolved in the secretion of insulin and in the function of the hormone.

According to the present invention, minerals can be provided asinorganic compounds, such as chlorides, sulfates, and the like. Inaddition, some minerals can be provided in more bioavailable forms, suchas amino acid chelates, which are well known in the art. U.S. Pat. No.5,292,538. Examples of minerals that can be provided as amino acidchelates include calcium, magnesium, manganese, zinc, iron, boron,copper, molybdenum, and chromium. Still further, minerals can beprovided as deep sea minerals.

Additional elements of the presently disclosed compositions may includefruit flavorings and colorings, such as grape and raspberry in smallamounts. Sweeteners, such as momordica fruit may also be included.Components to enhance absorption into the body, such as black or Sichuanpepper extracts may be added. Preservatives, such as sodium benzoate orpotassium sorbate may also be included. Substantially pure water, suchas deionized water, is also an important ingredient of the liquidmixture.

In one embodiment, the dietary supplement may be provided as anutritional drink or beverage. The supplement may also be dried into apowder and provided as a freeze dried or spray dried powder, capsule, ortablet. An illustrative beverage supplement is now described in greaterdetail.

Starting with the fucoidan-containing puree described above, juices orconcentrates to provide a high oxygen radical absorbance capacity(ORAC), such as acai fruit, grape, and blueberry are added. Also, fruitflavoring and colorings, such as grape and raspberry; minerals, such asdeep sea minerals; sweeteners, such as momordica fruit; pepper forflavor enhancement and to enhance absorption into the body, such asblack pepper; preservative, such as sodium benzoate or potassiumsorbate; and deionized water are added to the mixture. Next, the mixtureis sterilized by pasteurization or other heating techniques. Althoughpasteurization (at least 87.8° C. or 190° F.) effectively eliminatespathogenic microorganisms, sterilization at higher temperatures maybeneeded to eliminate all microorganisms.

In achieving the necessary sterilization, two different sterilizationprocesses are typically used. Using the HTST (high temperature shorttime) process, the mixture may be raised to about 85° C. (185° F.) forabout 20-30 seconds. Alternately, the ultra-high temperature (UHT)process involves raising the temperature of the mixture to about 140.6°C. (285° F.) for about 4-6 seconds. In either process, immediately afterthe heating step, the temperature is rapidly lowered to at least ambienttemperatures of about 21.1-26.7° C. (70-80° F.). Alternately, themixture may be chilled down to about 4.4° C. (40° F.).

Heating of the mixture may be accomplished by direct or indirectheating. For example, the mixture may be heated by direct contact withsteam or indirectly by a selected type of heat exchanger.

The sterilized blend may then be poured into containers, using ahot-fill or cold-fill method. In the hot-fill process, the product isfirst heated to temperatures for pasteurization, HTST, or UHT. Then itis poured into containers at elevated temperatures to kill anymicroorganisms inside the container. The use of preservatives, such assodium benzoate and potassium sorbate are normally used. The pH isusually maintained below 4.4, possibly using acids such as lemon juiceor vinegar. After filling, the bottles may be cooled slowly by a watermist. Filling of containers is done by aseptic processing and packagingmethods, which are well known in the art.

In the cold-fill process, after pasteurization or sterilizationtemperatures are reached, the product is immediately cooled to aboutroom temperature prior to bottling, using aseptic processing andpackaging techniques. Immediate cooling allows less vitamin degradationand variations in flavor that may be found in the hot-fill process.Thus, in cold-fill processing the flavor may be cleaner and fresher.Preservatives are usually included to control the growth of yeast,molds, and bacteria.

The cold-fill process is compatible with use of high-densitypolyethylene (HDPE) or polyethylene terephthalate (PET) bottling, so asto not compromise the integrity of the bottle structure. The bottles maybe 500 ml bottles, capable of containing about 660 grams per bottle. Thesize would provide sufficient beverage for 30 days, if a recommendeddosage is about 22 grams per day.

Solid dosage forms according to the present invention can be made in theform of powders, tablets, and capsules according to methods well knownin the art. For example, powders can be made by drying the fucoidanpreparation, and then mixing the dried fucoidan with other driedingredients. Alternatively, the fucoidan preparation can be mixed withother ingredients, and then the mixture is dried into a powder.Illustrative methods of drying include spray drying and freeze drying.The powder can then be ingested by suspending or dissolving it in aliquid and drinking the resulting suspension or solution. Illustrativeliquids that can be used for this purpose include water, juice, and thelike. The powder can also be compressed into tablets or loaded intocapsules. Tablets or capsules are typically swallowed with water orother liquid. Liquid dietary supplements can also be encapsulated andtaken in such a solid dosage form.

Examples

The following are examples of the preparation of seaweed to provide afucoidan puree for use in dietary supplements, and dietary supplementformulations prepared from the fucoidan puree. These examples are merelyillustrative and are not meant to be limiting in any way.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims, rather than by the description or examples. Allchanges that come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

Example 1 Preparation of Fucoidan Puree Composition

Tongan limu moui seaweed was manually harvested, cleaned to removeextraneous material, frozen, and shipped to a processing plant. At theplant, the frozen seaweed was thawed, weighed, and placed in a stainlesssteel mixer with aqueous buffer and optionally sulfuric acid accordingto any of the sets of conditions set out in Table 1. The ingredientswere then mixed at 50-75 rpm with a medium shear mixer (propeller type).While mixing, the mixture was heated to 37° C. to 95° C. for a selectedperiod of time (usually 5 min to 8 hr). At that point, heating wasdiscontinued, but mixing was continued for 0.5-10 hours to dissipateheat and micronize the seaweed strands. The cooled mixture was thenfiltered to remove insoluble material, and the filtrate was covered andmixed at room temperature for about 4-72 hours. The pH of the resultingpuree was determined to be about pH 2.0 to 4.0, and refractometrytypically showed a Brix value of 2-4. The puree comprising partiallyhydrolyzed fucoidan was then frozen and stored. If sulfuric acid wasadded during hydrolysis, the partially hydrolyzed fucoidan wassulfonated.

TABLE1 Trials I II III IV V VI VII pH 2.0-2.4 2.2-2.5 2.4-2-7 2.6-3.02.9-3.2 3.2-3.6 3.6-4.0 sulfuric acid — 0.01 N — 0.001 N 0.004 N — 0.001seaweed 20 wt % 10 wt % 25 wt % 40 wt % 33 wt % 15 wt % 42 wt % temp 37°C. 42° C. 50° C. 60° C. 75° C. 80° C. 95° C. heating time 5 hr 4 hr 4 hr3 hr 35 min 20 min 15 min filtrate 24 hr, 16 hr, 72 hr, 24 hr, 48 hr, 36hr, 8 hr, mixing 37° C. 37° C. 22° C. 22° C. 22° C. 22° C. 22° C.

Example 2 Preparation of Fucoidan Beverage

Fucoidan puree prepared according to the procedure of Example 1 wasthawed and then mixed with other ingredients according to the presentinvention as set out in Tables 2 and 3, where amounts are in parts byweight. These ingredients were blended thoroughly and then sterilizedand bottled in by aseptic processing and packaging methods according toany of the conditions set out in Table 4.

TABLE 2 Formulation Number 1 2 3 4 5 6 fucoidan 20 25 30 35 40 45 water80 75 64 64.2 54.63 45.62 grape 6 blueberry 4 acai 0.5 raspberry 2.5blackberry 1.5 strawberry 0.5 plum orange cherry 4 kiwi currant 1elderberry black currant cranberry deep sea 0.5 0.2 minerals momordica0.2 0.25 0.1 sodium 0.08 0.05 benzoate potassium 0.1 sorbate black 0.050.01 0.02 pepper Sichuan 0.02 0.03 pepper

TABLE 3 Formulation Number 7 8 9 10 11 12 fucoidan 0.5 8 13 17 19 22water 86.17 85.06 83.63 76.65 72.72 69.67 grape 2 5.7 5.5 blueberry 4.21.5 acai 0.5 0.1 0.3 0.5 raspberry 0.3 .3 blackberry 0.1 strawberry 1.00.8 plum 3.5 orange 10 cherry kiwi 3 0.4 currant elderberry 0.3 black0.5 currant cranberry 2.4 deep sea 0.33 0.4 0.23 0.29 0.31 mineralsmomordica 0.12 0.5 0.17 0.16 sodium 0.12 0.15 0.18 0.16 0.06 benzoatepotassium 0.08 0.2 0.04 0.11 sorbate black 0.005 0.01 0.14 0.01 pepperSichuan 0.005 0.02 0.015 pepper

TABLE 4 Condition No. Sterilization Bottling I  62.8° C., 30 min hotfill II  71.7° C., 15 sec hot fill III  93.3° C., 10 sec hot fill IV 96.0° C., 10 sec hot fill V  62.8° C., 30 min cold fill VI 140.6° C., 6sec cold fill

Example 3

About 70 parts by weight of fucoidan puree prepared according to theprocedure of Example 1 is mixed with about 99 parts by weight ofdistilled water, about 20 parts by weight of Concord grape extract,about 2 parts by weight of deep sea minerals, about 1 part by weight ofmomordica, and about 1 part by weight of black pepper extract. Theresulting mixture is spray dried into a powder and packaged for storageand distribution.

Example 4

The procedure of Example 3 is followed except that the powder isencapsulated in gelatin capsules.

Example 5

The procedure of Example 3 is followed except that the powder is mixedwith selected amounts of diluents, binders, lubricants, disintegrators,colors, flavors, and sweetening agents and then compressed into tablets.

1. A dietary supplement comprising about 0.5 to about 70 parts by weightof partially hydrolyzed fucoidan and about 30 to about 99.5 parts byweight of water.
 2. The dietary supplement of claim 1 further comprisingabout 0.5 to about 20 parts by weight of a nutraceutical ingredienthaving a high ORAC value.
 3. The dietary supplement of claim 2 whereinthe nutraceutical ingredient having a high ORAC value comprises grapeconcentrate.
 4. The dietary supplement of claim 2 wherein thenutraceutical ingredient having a high ORAC value comprises blueberryconcentrate.
 5. The dietary supplement of claim 2 wherein thenutraceutical ingredient having a high ORAC value comprises acai fruitconcentrate.
 6. The dietary supplement of claim 2 wherein thenutraceutical ingredient having a high ORAC value is a member selectedfrom the group consisting of grape concentrate, blueberry concentrate,acai fruit concentrate, raspberry concentrate, blackberry concentrate,strawberry concentrate, plum concentrate, orange concentrate, cherryconcentrate, kiwi fruit concentrate, currant concentrate, elderberryconcentrate, black currant concentrate, cranberry concentrate,mangosteen, noni, aronia, wolfberry, anthocyanidins, curcuminoids, andmixtures thereof.
 7. The dietary supplement of claim 1 wherein thepartially hydrolyzed fucoidan is sulfonated.
 8. The dietary supplementof claim 1 wherein the fucoidan is from Tongan limu moui seaweed.
 9. Thedietary supplement of claim 1 wherein the fucoidan is from Japanesemozuku or kombu seaweeds, or comprises a mixture of fucoidans fromJapanese mozuku and kombu seaweeds.
 10. The dietary supplement of claim1 further comprising about 0.01 to about 2 parts by weight of minerals.11. The dietary supplement of claim 10 wherein the minerals comprisedeep sea minerals.
 12. The dietary supplement of claim 1 furthercomprising about 0.01 to about 1 parts by weight of a flavoring agent.13. The dietary supplement of claim 1 further comprising about 0.01 toabout 1 parts by weight of a preservative.
 14. The dietary supplement ofclaim 13 wherein the preservative comprises sodium benzoate.
 15. Thedietary supplement of claim 1 further comprising about 0.001 to about 1parts by weight of pepper extract.
 16. The dietary supplement of claim15 wherein the pepper extract comprises black pepper.
 17. The dietarysupplement of claim 15 wherein the pepper extract comprises Sichuanpepper.
 18. A dietary supplement comprising about 0.5 to about 70 partsby weight of partially hydrolyzed fucoidan, about 0.5 to about 20 partsby weight of a nutraceutical ingredient having a high ORAC value andabout 10 to about 99 parts by weight of water.
 19. The dietarysupplement of claim 18 wherein the nutraceutical ingredient having ahigh ORAC value comprises grape concentrate.
 20. The dietary supplementof claim 18 wherein the nutraceutical ingredient having a high ORACvalue comprises blueberry concentrate.